ArticleProceedings of the National Academy of Sciences of the United States of America2008
Adaptive mutations in the signal peptide of the type 1 fimbrial adhesin of uropathogenic Escherichia coli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Parallel evolutionary trajectories rewire enteropathogenicGut microbes · 2026Article
- Polymicrobial urine cultures: reconciling contamination with the urobiome while recognizing the pathogens.Frontiers in cellular and infection microbiology · 2025Review
- Nature of the Interaction of Alpha-D-Mannose and Escherichia coli Bacteria, and Implications for its Regulatory Classification. A Delphi Panel European Consensus Based on Chemistry and Legal Evidence.Therapeutic innovation & regulatory science · 2023Article
- Pathogenicity assessment of Shiga toxin-producingFrontiers in microbiology · 2023Article
- Article
- Article
- Conditional Function of Autoaggregative Protein Cah and CommonApplied and environmental microbiology · 2018Article
- Adaptation of Escherichia coli traversing from the faecal environment to the urinary tract.International journal of medical microbiology : IJMM · 2016Article
- An Environmental Shiga Toxin-Producing Escherichia coli O145 Clonal Population Exhibits High-Level Phenotypic Variation That Includes Virulence Traits.Applied and environmental microbiology · 2016Article
- Suppression of type 1 pilus assembly in uropathogenic Escherichia coli by chemical inhibition of subunit polymerization.The Journal of antimicrobial chemotherapy · 2014Article
- Article
- Point mutations in FimH adhesin of Crohn's disease-associated adherent-invasive Escherichia coli enhance intestinal inflammatory response.PLoS pathogens · 2013Article
- Combinatorial small-molecule therapy prevents uropathogenic Escherichia coli catheter-associated urinary tract infections in mice.Antimicrobial agents and chemotherapy · 2012Article
- Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection.FEMS microbiology reviews · 2012Review
- Lead optimization studies on FimH antagonists: discovery of potent and orally bioavailable ortho-substituted biphenyl mannosides.Journal of medicinal chemistry · 2012Article
- High-resolution two-locus clonal typing of extraintestinal pathogenic Escherichia coli.Applied and environmental microbiology · 2012Article
- Treatment and prevention of urinary tract infection with orally active FimH inhibitors.Science translational medicine · 2011Article
- Uropathogenic Escherichia coli P and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction.PLoS pathogens · 2011Article
- Population structure of gut Escherichia coli and its role in development of extra-intestinal infections.Iranian journal of microbiology · 2010Article
- Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Signal peptides (SPs) are critical for protein transport across cellular membranes, have a highly conserved structure, and are cleaved from the mature protein upon translocation. Here, we report that naturally occurring mutations in the SP of the adhesive, tip-associated subunit of type 1 fimbriae (FimH) are positively selected in uropathogenic Escherichia coli. On the one hand, these mutations have a detrimental effect, with reduced FimH transport across the inner membrane, fewer FimH and fimbriae expressed on the bacterial surface, and decreased bacterial adhesion under flow conditions. On the other hand, the fimbriae expressed by the mutants are significantly longer on average, with many fimbriae able to stretch to >20 microm in length. More surprisingly, the SP mutant bacteria display an increased ability to resist detachment from the surface upon a switch from high to low flow. This functional effect of longer fimbriae highlights the importance of the nonadhesive fimbrial rod for adhesive function. Also, whereas bacterial adhesion to bladder epithelial cells was preserved in most mutants, binding to and killing by human neutrophils was decreased, providing an additional reason the SP mutations are relatively common among uropathogenic strains. Thus, this study demonstrates how mutations in an SP, while decreasing transport function and not affecting the final structure of the translocated protein, can lead to functional gains of the extracellular organelles that incorporate the protein and overall adaptive changes in the organism's fitness.
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